Departamento de Microbiología, Laboratorio de Inmunología y Medicina Traslacional, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Colombia.
Departamento de Movimiento Corporal Humano, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Colombia.
PLoS One. 2023 Feb 10;18(2):e0280851. doi: 10.1371/journal.pone.0280851. eCollection 2023.
Breast cancer is the leading cause of cancer deaths in women worldwide. It has been observed that the incidence of breast cancer increases linearly with age after 45, which suggest a link between cancer, aging, and senescence. A growing body of evidence indicates that the immunosuppressive tumor network in breast cancer patients can lead to T-cell exhaustion and senescence. Cytotoxic chemotherapy is a common treatment for many cancers, and it is hypothesized that its efficacy may be related to immune activation. However, the effects of neoadjuvant chemotherapy on T-cell dysfunction in breast cancer patients are not fully understood. This study aimed to evaluate the impact of neoadjuvant chemotherapy on the expression of exhaustion and senescence markers in T cells in women with breast cancer. Our results showed that T cells from breast cancer patients have a reduced ability to respond to stimulation in-vitro and an increased expression of senescence and exhaustion-associated markers, such as TIM-3, LAG3, and CD57. Furthermore, we found that neoadjuvant chemotherapy has an immunomodulatory effect and reduces the expression of exhaustion markers. Our observations of the immune phenotype of T cells during neoadjuvant chemotherapy treatment highlight its ability to stimulate the immune system against cancer. Therefore, monitoring the response of T cells during chemotherapy may enable early prediction of clinical response.
乳腺癌是全球女性癌症死亡的主要原因。据观察，乳腺癌的发病率在 45 岁后呈线性增长，这表明癌症、衰老和衰老之间存在联系。越来越多的证据表明，乳腺癌患者的免疫抑制性肿瘤网络可导致 T 细胞耗竭和衰老。细胞毒性化疗是许多癌症的常用治疗方法，据推测其疗效可能与免疫激活有关。然而，新辅助化疗对乳腺癌患者 T 细胞功能障碍的影响尚不完全清楚。本研究旨在评估新辅助化疗对乳腺癌患者 T 细胞衰竭和衰老标志物表达的影响。我们的结果表明，乳腺癌患者的 T 细胞体外刺激反应能力降低，衰老和衰竭相关标志物（如 TIM-3、LAG3 和 CD57）的表达增加。此外，我们发现新辅助化疗具有免疫调节作用，可降低衰竭标志物的表达。我们在新辅助化疗治疗期间对 T 细胞免疫表型的观察突出了其刺激免疫系统对抗癌症的能力。因此，监测化疗期间 T 细胞的反应可能能够早期预测临床反应。
